Pulmonary infection with Pseudomonas aeruginosa is common in patients with cystic fibrosis and accounts for considerable morbidity and mortality. Current antibiotic therapy of pseudomonas lung infection is unsatisfactory, thus an evaluation of immunoprophylaxis with two currently available lipopolysaccharide pseudomonas vaccines is proposed. Since these vaccines are associated with endotoxin-like side effects, it would be important to establish whether they are of potential value in inducing specific protection in the respiratory tract before clinical trails in cystic fibrosis patients are undertaken. A pre-clinical evaluation of these vaccines will be undertaken using an established guinea pig model of fatal pseudomonas pneumonia. In addition, a recently developed model of fatal pseudomonas lung infection in guinea pigs will be utilized to more closely mimic the chronic infection seen in cystic fibrosis patients. The ability of pseudomonas vaccines to increase survival from pseudomonas lung infection, plus the capacity of vaccination to decrease lung tissue damage and augment clearance of pseudomonas from lung tissues will be determined. Finally, the mechanisms by which vaccines increase local pseudomonas immunity in the respiratory tract will be analyzed. The ability of pseudomonas vaccines to activate macrophages directly or with the aid of sensitized lymphocytes plus the value of vaccine-induced opsonic antibodies to increase pseudomonas clearance by alveolar macrophages will be studied. A correlation between in vivo respiratory protection and in vitro immune mechanisms can thus be made for pseudomonas vaccines. If significant protective benefits from pseudomonas vaccine can be demonstrated in this experimental model, future trials of immunoprophylaxis in cystic fibrosis patients should be considered.